Patterns of left ventricular response in essential hypertension.
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BACKGROUND: The purpose of this study was to investigate the prevalence of skeletal muscle atrophy and its relation to exercise intolerance and abnormal muscle metabolism in patients with heart failure (HF). METHODS AND RESULTS: Peak VO2, percent ideal body weight (% IBW), 24-hour urine creatinine (Cr), and anthropometrics were measured in 62 ambulatory patients with HF. 31P magnetic resonance spectroscopy (MRS) and imaging (MRI) of the calf were performed in 15 patients with HF and 10 control subjects. Inorganic phosphorus (Pi), phosphocreatine (PCr), and intracellular pH were measured at rest and during exercise. Calf muscle volume was determined from the sum of the integrated area of muscle in 1-cm-thick contiguous axial images from the patella to the calcaneus. A reduced skeletal muscle mass was noted in 68% of patients, as evidenced by a decrease in Cr-to-height ratio of less than 7.4 mg/cm and/or upper arm circumference of less than 5% of normal. Calf muscle volume (MRI) was also reduced in the patients with HF (controls, 675 +/- 84 cm3/m2; HF, 567 +/- 112 cm3/m2; p less than 0.05). Fat stores were largely preserved with triceps skinfold of less than 5% of normal and/or IBW of less than 80% in only 8% of patients. Modest linear correlations were observed between peak VO2 and both calf muscle volume per meter squared (r = 0.48) and midarm muscle area (r = 0.36) (both p less than 0.05). 31P metabolic abnormalities during exercise were observed in the patients with HF, which is consistent with intrinsic oxidative abnormalities. The metabolic changes were weakly correlated with muscle volume (r = -0.42, p less than 0.05). CONCLUSIONS: These findings indicate that patients with chronic HF frequently develop significant skeletal muscle atrophy and metabolic abnormalities. Atrophy contributes modestly to both the reduced exercise capacity and altered muscle metabolism.
In a prospective blinded trial, 24-hour continuous electrocardiographic monitoring for silent ischemia was used to try to identify rehabilitation patients at risk for cardiac complications. Five of 42 patients had episodes of silent ischemia, none of which occurred during physical therapy sessions. One of these patients had syncope while wearing the Holter; none of the other four patients had significant cardiac complications during their rehabilitation, and all were discharged home. None of the patients without ischemia on the monitor had complications, but two patients of 14 whose ECGs precluded monitoring for ischemia had complications. In addition, six patients had episodes of nonsustained asymptomatic ventricular tachycardia, 12 had episodes of supraventricular tachycardia, and four had significant ventricular ectopy, all without clinical significance. Despite the apparent high sensitivity and specificity of the technique, the positive predictive value of monitoring eligible patients for silent ischemia was 20%. We conclude that ambulatory electrocardiographic monitoring for silent ischemia or ectopy has limited clinical utility in the rehabilitation population.
Transesophageal echocardiography permits measurement of the pulmonary artery diameter (two-dimensional echocardiography) and pulmonary artery blood flow velocity (pulsed-wave Doppler). These measurements considered with the heart rate allow for the determination of pulmonary artery blood flow, which is equivalent to cardiac output. This study compared the precision of transesophageal Doppler-derived cardiac output (DdCO) with the precision of thermodilution cardiac output (TdCO) and examined the agreement between DdCO and TdCO in 33 cardiac surgical patients. The proximal pulmonary artery diameter was measured in triplicate during systole and end expiration, and the local blood flow velocity was recorded on video tape. The instantaneous pulmonary artery blood flow velocity (centimeters per second) for three random cardiac beats was integrated with respect to time. DdCO was calculated as the product of the flow velocity integral (centimeters per beat), heart rate (beats per min), and the mean cross-sectional area (centimeters squared) of the main pulmonary artery. At the same time that the velocity recordings were made, three serial determinations of TdCO were made by an independent observer. Pulmonary blood flow could be measured in 25 of the 33 patients. The anatomical relationship among the esophagus, the left main stem bronchus, and the pulmonary artery did not allow adequate imaging of the pulmonary artery in 8 (24%) of the patients. A total of 45 sets of triplicate measurements were made. The range of cardiac outputs encountered was 1.7-6.6 l.min-1 by TdCO and 1.5-6.9 l.min-1 by DdCO. The 95% confidence limits for the difference between the two methods (agreement) was 0.030 +/- 0.987 l.min-1.(ABSTRACT TRUNCATED AT 250 WORDS)
Cine magnetic resonance imaging (MRI) displays cardiac flow in cine loop fashion on multiple tomographic sections. Since laminar flow is easily distinguished from turbulent flow, cine MRI may be uniquely suited to the study of valvular regurgitation: the entire cardiac volume can be sampled and the regurgitant jet at the valve plane can be depicted. We therefore assessed aortic regurgitation (AR) by cine MRI in 35 patients and 11 normal volunteers and compared results to pulsed (n = 32) or color flow Doppler (n = 14). The extent of the flow disturbance was estimated for both cine MRI and Doppler by indexing the size of the maximal, single plane regurgitant jet area (JA) to the left ventricular (LV) area. Cine MRI JA/LV ratio compared well with pulsed (r = 0.81) and color flow (r = 0.88) Doppler; classification as mild (less than 20%), moderate (20-40%), and severe (greater than 40%) AR by both methods was identical in 43 of 46 cases with no differences of more than one grade. Overall sensitivity and specificity of cine MRI, compared to Doppler, were 94 and 95%, respectively. Cine MRI also depicted the regurgitant jet at the valve plane in 11 patients. Thus planar analysis of cine MRI images in patients with AR provides a semiquantitative assessment of the AR flow disturbance which is similar to Doppler but, in addition, can image the entire cardiac volume and the regurgitant jet at the valve plane.
BACKGROUND: Conventional cardiac imaging methods do not depict true segmental myocardial shortening, since they cannot determine segment length between fixed points in the myocardium. METHODS AND RESULTS: We used electrocardiographically gated magnetic resonance imaging with spatial modulation of magnetization to noninvasively "tag" the myocardium with dark stripes at uniform 7-mm intervals center to center at end diastole. We then determined end-systolic stripe separation and thereby calculated circumferential shortening. When end systole was not reached in the first image series, a second temporally overlapped series starting in late systole was used to determine late-systolic shortening. Septal, anterior, lateral, and inferior segments were assessed at endocardium, midwall, and epicardium on five midventricular short-axis sections each in 10 normal volunteers. A transmural gradient in circumferential shortening was observed, with the percentage of endocardial segment shortening consistently greater than epicardial segment shortening (epicardial, 22 +/- 5%; midwall, 30 +/- 6%; and endocardial, 44 +/- 6%; p less than 0.0001 by analysis of variance). Circumferential shortening varied from apex to base with slices closer to the base of the left ventricle showing less shortening at the midwall (28 +/- 9%) and endocardium (39 +/- 6%) than more apical slices at the midwall (34 +/- 13%) and endocardium (49 +/- 9%) (p less than 0.05 and p less than 0.01, respectively, by analysis of variance). CONCLUSIONS: Transmural and longitudinal heterogeneity of circumferential shortening is present in the normal human left ventricle. Magnetic resonance imaging with spatial modulation of magnetization is a powerful new tool for assessment of circumferential shortening and provides information unobtainable with conventional imaging methods.
To determine correlates of acute vasodilator responsiveness in primary pulmonary hypertension, we retrospectively studied 25 patients, comparing 41 resting echo/Doppler and nine resting catheterization variables with the maximal reduction in pulmonary vascular resistance achieved during vasodilator trials. Twelve vasodilators were tested (mean, 5.6 drugs per patient; range, three to eight). Eight patients were vasodilator responsive, as defined by a reduction in pulmonary vascular resistance greater than or equal to 30 percent in response to at least one agent. Univariate and multivariate analyses revealed only Doppler pulmonic peak flow velocity to be an independent correlate of responsiveness (p less than 0.05). Responders differed from nonresponders in having a higher Doppler pulmonic peak flow velocity (PV) (SD 81 +/- 24 vs 64 +/- 15 cm/s; p = 0.05), lower mean right atrial pressure (RAP) (6 +/- 4 vs 13 +/- 7 mm Hg; p = 0.04), and longer median survival (37 vs 5 months; p = 0.03). Seven of eight responders had RAP less than or equal to 10 mm Hg, and all responders had PV greater than 60 cm/s. Seven of ten patients with both RAP less than or equal to 10 and PV greater than 60 and one of the 15 remaining patients were vasodilator responsive (p less than 0.001). Thus, echo/Doppler and invasive hemodynamic parameters correlate with acute vasodilator responsiveness in primary pulmonary hypertension. Patients with low PV and high RAP values were almost never vasodilator responsive. Doppler pulmonic peak velocity and mean RAP may be useful in identifying patients most likely to respond to acute vasodilator trials and those in whom testing is unlikely to yield positive results.
It is likely that, as the field progresses, cardiac magnetic resonance imaging (MRI) will become the definitive reference imaging method for evaluation of myocardial function. The first phase of development in the field has emphasized replication and improvement of commonly used methods for analysis of global ventricular pump function, global ventricular mechanics, and regional myocardial performance. Thus, validated MRI methods exist for assessment of ventricular end-diastolic and end-systolic volume and ejection fraction. Similarly, standard methods for evaluation of myocardial mean wall stress can be applied to evaluation of afterload as a determinant of ventricular performance. Regional function of myocardium can be evaluated using either regional endocardial motion or regional wall thickening. In addition, recent development of novel methods for assessment of local myocardial motion by tracking motion at fixed points in the tissue over the cardiac cycle has attracted interest from the cardiovascular research community. These methods, such as radial stripe myocardial tagging and spatial modulation of magnetization, have already provided unique and incisive new information on segmental myocardial performance in normal and diseased hearts in experimental models and in man. The most important limitation of cardiac MRI for assessment of cardiac function continues to be long image acquisition times. The advent of real time methods, with further development, should address this problem.
We used cine magnetic resonance imaging (MRI) to assess mitral regurgitation (MR) in 40 patients with coronary and/or valvular disease and 10 normal subjects and compared results to pulsed (n = 30) or color flow Doppler mapping (n = 20). Mitral regurgitation produced a dynamic signal void in the left atrium in systole in 15 of 16 patients with MR by pulsed Doppler and in an additional 15 of 16 patients whose MR was demonstrated by color flow Doppler. There were no false positives (sensitivity 94%, specificity 100% for both). The ratio of single-plane, maximal jet area to left atrial area was used to grade MR severity with mild defined as less than 20%, moderate between 20 and 40% and severe greater than 40%. Cine MRI classification was identical to pulsed Doppler echocardiography in 26 of 30 patients and to color flow Doppler in 16 of 20 patients with no differences of greater than 1 grade. Cine MRI consistently depicted smaller flow disturbances than pulsed Doppler (slope = 0.65) or color flow Doppler (slope = 0.60). Nonetheless, the cine MRI area ratio correlated well with pulsed Doppler (r = 0.78) and with color flow Doppler (r = 0.74). Thus, planar analysis of cine MRI in patients with MR of varying severity gave results that were similar to Doppler echocardiography. At present, for routine clinical assessment of MR, the benefits of cine MRI may be limited to patients in whom transthoracic Doppler echocardiography is not adequate.
The effects of imaging view and sample volume location on tricuspid velocimetry and of heart rate and aging on mitral and tricuspid inflow were evaluated in 41 normal subjects aged 20 to 76 years. Pulsed Doppler recordings were obtained in the parasternal short-axis, right ventricular inflow and apical 4-chamber views at the level of the tricuspid and mitral anuli and 1 cm caudad and 1 cm cephalad to the tricuspid anulus in the 4-chamber apical view. The right ventricular filling pattern was not affected by imaging view. However, placement of the sample volume 1 cm cephalad resulted in a 16% reduction (p less than 0.01) in early velocity with a 9% increase in atrial filling fraction. Conversely, late velocity was 11% higher (p less than 0.05) at the anular level versus the other locations. Right and left ventricular filling velocities were modestly related (r = 0.50 to 0.63). Relations between age and tricuspid late velocity, velocity ratio and atrial filling fraction were weaker (r = 0.34 to 0.47; all p less than 0.05) than those between age and mitral variables (r = 0.59 to 0.74. Also, aging had a greater effect on mitral than tricuspid late velocity (i.e., a steeper slope; p less than 0.01). Tricuspid late velocity and atrial filling fraction were each modestly inversely related to RR interval (r = -0.48, r = -0.54; p less than 0.01). Thus, tricuspid velocity is affected by sample volume location, aging and heart rate, but not imaging view. Sample volume location, heart rate and age should be considered when evaluating right ventricular inflow parameters.
To examine the functional consequences of the greater increase in right ventricular work with exercise, the effects of prolonged exercise on the right and left heart chambers were compared in 41 athletes before, at the finish (13 min) and after recovery (28 h) from the Hawaii Ironman Triathlon (3.9 km swim, 180.2 km bike ride, 42.2 km run). Two-dimensional and Doppler echocardiograms were analyzed for left and right atrial and ventricular areas at end-diastole and end-systole, right and left ventricular inflow velocities and mitral and tricuspid regurgitation. After exercise, left ventricular and left and right atrial sizes were reduced, whereas right ventricular size increased (diastole: 21.4 to 24.2 cm2; systole: 15.8 to 18.2 cm2; p less than 0.01). The emptying fraction of all chambers was unchanged. Left but not right ventricular inflow showed an increase in peak velocity of rapid filling, whereas both atrial systolic velocities increased (26 to 38 cm/s tricuspid; 38 to 54 cm/s mitral; both p less than 0.01). Overall, the right ventricular early to atrial velocity ratio was reduced after exercise (1.56 to 1.17; p less than 0.05) and the left ventricular pattern was unchanged. The prevalence of tricuspid regurgitation was statistically unchanged (86% to 52%), although that of mitral regurgitation was greatly reduced (76% to 0%). Changes in all variables returned toward prerace values during recovery. Thus, in highly trained athletes, prolonged exercise causes differing responses of the right and left ventricles. These differences may be due to changes in right ventricular function, shape or compliance.
Cine gradient-recalled magnetic resonance (MR) imaging, which has flow sensitivity and high temporal resolution, may potentially yield both morphologic and dynamic flow-related information in the pulmonary vasculature. The authors used this modality to evaluate pulmonary vessels in 12 healthy subjects and in 14 patients with a variety of cardiopulmonary disorders. Normal pulmonary arteries and veins were characterized by distinctive signal intensity and diameter variations as well as motion of the vessels during the cardiac cycle. Patients with pulmonary arterial hypertension demonstrated loss of the normal pulsatile systolic increase and diastolic decline in velocity-related signal intensity and in diameter of the proximal pulmonary arteries. Disorders of pulmonary venous signal and diameter profiles during the cardiac cycle, which show a characteristic biphasic pattern in healthy subjects, were identified in five patients with mitral valvular disease. These initial results indicate that cine MR imaging techniques hold promise in the evaluation of pathophysiologic conditions in the pulmonary circulation.
To assess the effects of exercise training on the prevalence of valvular regurgitation, 2-dimensional echocardiography and Doppler flow mapping were performed in 45 athletes and 26 sedentary control subjects of similar age and sex. Mitral, tricuspid, aortic and pulmonic regurgitations were sought in all possible views and mitral and tricuspid flow velocities were recorded. Mitral and tricuspid anulus diameters and the maximal areas of regurgitant flow were planimetered. Regurgitation of at least one of the cardiac valves was found in 91% of athletes but in only 38% of control subjects (p less than 0.001). Mitral and tricuspid regurgitation occurred more commonly in athletes than in control subjects (mitral 69 vs 27%; tricuspid 76 vs 15%). The prevalence of aortic and pulmonic regurgitation was similar. Although athletes and sedentary normal subjects differed with respect to heart rate, right and left ventricular filling patterns and tricuspid and mitral anulus diameters, none of these variables was related to the presence or severity of regurgitation. Thus, exercise training is associated with an increased prevalence of mitral and tricuspid regurgitation and altered ventricular inflow patterns. The mechanism of these findings is unclear. Multivalvular regurgitation is common in athletes and does not imply structural valvular abnormalities.
Because idiopathic dilated cardiomyopathy is characterized by elevated wall stress and a more spherical left ventricle, the relations among shape, afterload and survival were examined. Thirty-six patients with cardiomyopathy were prospectively studied by two-dimensional echocardiography. Data included echocardiographic short- and long-axis cavity dimensions, their ratio and, with cuff systolic blood pressure, meridional and circumferential end-systolic stress and their ratios. Survivors (n = 16) were followed up for 52 months (range 40 to 76); nonsurvivors (n = 20) died an average of 11 months after study. Survivors had a smaller left ventricular end-diastolic short-axis dimension (6.4 versus 7.1 cm, p less than 0.03) but a similar long-axis length (8.6 versus 8.3 cm). However, overall cavity shape or the ratio of short- to long-axis end-diastolic dimensions was more spherical in those with poorer survival (ratio 0.76 versus 0.68, p less than 0.02). Meridional and circumferential end-systolic stresses were similar in the two groups, but stress was more evenly distributed in the long- and short-axis planes in nonsurvivors (meridional/circumferential stress ratio 0.57 versus 0.52 in survivors, p less than 0.05). Improved survival was associated with an end-diastolic short-axis dimension less than 7.63 cm, a short- to long-axis ratio less than 0.76 and a meridional to circumferential stress ratio less than 0.54. Life table analysis revealed a 28% mortality rate in patients with all three of these characteristics compared with 100% in patients with none. Survivors and nonsurvivors did not differ in systolic cavity dimension, wall thickness, relative wall thickness, cavity volume, percent posterior wall thickening or fractional shortening.(ABSTRACT TRUNCATED AT 250 WORDS)
To examine the time course of the functional consequences of progressive left ventricular hypertrophy, diastolic left ventricular inflow and wall thinning variables were analyzed in 13 dogs before and 2, 4, 8 and 12 weeks after creation of perinephritic hypertension. Left ventricular echocardiograms were digitized for dimensions, mass and peak rates of wall thinning (-dh/dt/h) and cavity enlargement (dD/dt/D). Doppler recordings of left ventricular inflow were analyzed for peak early (E) and late (A) diastolic inflow velocities, their ratio and atrial filling fraction. At 2 weeks, systolic blood pressure increased from 151 to 233 mm Hg, wall stress from 52 to 80 kdynes/cm2 and posterior wall thickness from 0.68 to 0.84 cm (all p less than 0.05). Left ventricular mass increased from 90 to 115 g over 12 weeks (p less than 0.05). Heart rate, cavity size and systolic shortening were unchanged at all data points. Diastolic abnormalities accompanied the developing hypertrophy and included impairment of early function, as demonstrated by a peak rate of wall thinning, from -13.4 to -8.9 l/s at 2 weeks (p less than 0.05), increased dependence on atrial systolic filling, a decrease in E/A from 1.68 to 1.29 at 4 weeks (p less than 0.05) and an increase in atrial filling fraction from 30% to 43% at 8 weeks (p = NS). Thus, diastolic dysfunction is an early consequence of experimental left ventricular hypertrophy. Different aspects of diastolic impairment are sensitively reflected by echocardiographic Doppler recordings, suggesting that these methods should be useful for the detection of diastolic dysfunction in human patients.
The rationale for intermittent nitrate therapy is based on the pathophysiology of nitroglycerin tolerance and the diurnal pattern of symptoms encountered in patients with chronic stable angina. Nitrate tolerance was first observed as tolerance to headache in industrial toxicology. When long-acting nitrates for chronic stable angina became available, similar tolerance was observed but not thought to indicate tolerance to a haemodynamic or therapeutic effect. Subsequently, Needleman and coworkers (J Pharmacol Exp Ther 1973; 187: 324) defined in vitro the phenomenology of vascular smooth muscle tolerance to nitroglycerin-induced relaxation and reversibility was demonstrated. More recently, a potential molecular explanation for nitrate tolerance has been proposed: sulfhydryl group depletion in smooth muscle cells resulting in reduced formation of S-nitrosothiols on nitrate exposure with resultant reduced activation of cyclic GMP. In vivo, other mechanisms, including fluid retention and neurohumoral responses to vasodilation may also be important. The first demonstration that nitrate tolerance affected the therapeutic efficacy of long-acting nitrates was reported by Parker and coworkers in 1982 (Circulation 1987; 76: 572-6). This landmark study was not given much credence at the time because it appeared to be in conflict with earlier reports. However, in the past 6 years development of tolerance has been demonstrated with a variety of oral nitrates, transdermal nitroglycerin and intravenous nitroglycerin. When plasma concentrations are held constant, tolerance to antianginal effects is demonstrable within 24h, but varies markedly in severity from individual to individual.(ABSTRACT TRUNCATED AT 250 WORDS)
To determine correlates of survival in primary pulmonary hypertension, we compared 41 echocardiography-Doppler and nine catheterization parameters with outcome in 26 patients. Mean follow-up was 19.7 months in survivors; mean survival was 4.8 months in 16 nonsurvivors. Cox life-table univariate analysis correlated two echocardiographic, three Doppler, and three catheterization variables with poor survival (p less than or equal to 0.05), and chi 2 analysis ensured the best critical values: severity of pericardial effusion, heart rate of more than 87 beats/min, pulmonic flow acceleration time of less than 62 msec, tricuspid early flow deceleration (T-DEC) equal to or less than -300 cm2/sec, mitral early flow-to-atrial flow velocity ratio (M-E/A) equal to or less than 1.0, catheterization cardiac index (CI) equal to or less than 2.3 l/min/m2, mean pulmonary artery pressure of more than 61 mm Hg, and diastolic pulmonary artery pressure of more than 43 mm Hg. Multivariate life-table analysis of noninvasive variables revealed the severity of pericardial effusion to be independently significant (p = 0.006), whereas analysis of catheterization variables revealed cardiac index to be independently significant (p = 0.014). Combined multivariate analysis did not differ from the noninvasive results alone. Categorical modeling of the eight significant variables split at their critical values (present or absent) revealed M-E/A, T-DEC, and CI to be independently significant by multivariate analysis (p = 0.0014). Analysis of the five echocardiography-Doppler variables alone revealed M-E/A, T-DEC, and heart rate to be independently significant (p = 0.0016). In both cases, mortality increased with the number of critical values reached.(ABSTRACT TRUNCATED AT 250 WORDS)
Cine magnetic resonance imaging (MRI) is a gradient-recalled, retrospectively gated, fast-scan technique that depicts laminar flowing blood as bright signal and has been proposed as a useful method for determination of coronary artery bypass graft (CABG) patency. Therefore, we performed a blinded prospective study to assess the value of cine MRI determination of CABG patency in 20 patients with 45 CABG proximal anastomoses who were undergoing repeat angiography. Ten normal subjects served as controls to define normal intrathoracic vascular patterns. There were 21 left anterior descending (LAD) grafts, of which four were left internal mammary (LIMA), 12 left circumflex (Cx), and 12 right coronary (RCA) grafts. After localizing spin-echo coronal images were obtained, multiple axial multislice interleaved cine MRI acquisitions, each consisting of two to four 5-10-mm-thick slices at eight to 24 frames per cardiac cycle, were obtained from the superior main pulmonary artery to the inferior left ventricle. Each acquisition took 5-8 minutes with a subsequent 5-10 minutes of computer image reconstruction. Total study time per patient was 50-75 minutes. Known to cine MRI interpreters were the original surgical CABG insertions but not the angiographic findings. A graft was called patent if a bright graft flow signal, not corresponding to a normal vessel, was identified on multiple frames at multiple levels abutting the great vessels or epicardial surface of the heart. Angiographically, there were 33 patent grafts, of which 29 were identified as patent by cine MRI (sensitivity, 88%).(ABSTRACT TRUNCATED AT 250 WORDS)